PMID- 32014588 OWN - NLM STAT- MEDLINE DCOM- 20201130 LR - 20201130 IS - 1095-9947 (Electronic) IS - 1050-4648 (Linking) VI - 99 DP - 2020 Apr TI - Characterization and bioactivity of grass carp (Ctenopharyngodon idella) interleukin-21: Inducible production and involvement in inflammatory regulation. PG - 19-26 LID - S1050-4648(20)30067-X [pii] LID - 10.1016/j.fsi.2020.01.059 [doi] AB - In mammals, interleukin 21 (IL-21) is a broad pleiotropic cytokine that plays critical roles in the development of several inflammatory and autoimmune diseases. In fish, functional information of Il-21 is limited, and its role in immune response is largely unknown. In the present study, we cloned a coding sequence of grass carp (Ctenopharyngodon idella) il21 gene (gcil21). To characterize the release patterns and biological activity of gcIl-21, we prepared recombinant gcIl-21 (rgcIl-21) and obtained the polyclonal antibody with gcIl-21 specificity. Western blotting analysis showed that in grass carp head kidney leukocytes (HKLs), gcIl-21 was undetected in culture supernatant of untreated cells but drastically induced by heat-killed Aeromonas hydrophila (A. hydrophila), uncovering the release features of gcIl-21 and its possible involvement in immune response. Subsequent functional experiments revealed that rgcIl-21 did not affect the mRNA expression of grass carp il1b and tgfb, but induced a strong expression of grass carp il10, and to a lesser extent of grass carp tnfa in HKLs, suggesting a dominant effect of gcIl-21 in modulating Il-10 signaling as seen in rainbow trout and mammals. Furthermore, in vivo studies showed that intraperitoneal injection of rgcIl-21 was able to increase the survival rate of grass carp infected with live A. hydrophila, and reduce the pathological responses caused by the same pathogenic bacteria in head kidney and intestine. Taken together, these results for the first time revealed the close relationship of fish Il-21 production and function with inflammatory responses, and highlighted its anti-bacterial and anti-inflammatory ability, thereby providing a new insight into host defense mechanisms in fish. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Zhang, Anying AU - Zhang A AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. FAU - Jian, Xiaoyu AU - Jian X AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. FAU - Wang, Dan AU - Wang D AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. FAU - Ren, Jingqi AU - Ren J AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. FAU - Wang, Xinyan AU - Wang X AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. FAU - Zhou, Hong AU - Zhou H AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. Electronic address: zhouhongzh@uestc.edu.cn. LA - eng PT - Journal Article DEP - 20200131 PL - England TA - Fish Shellfish Immunol JT - Fish & shellfish immunology JID - 9505220 RN - 0 (Fish Proteins) RN - 0 (Interleukins) RN - 0 (Recombinant Proteins) RN - 130068-27-8 (Interleukin-10) RN - MKM3CA6LT1 (interleukin-21) SB - IM MH - Aeromonas hydrophila/immunology MH - Animals MH - Bacterial Infections/immunology/*veterinary MH - Carps/*immunology/microbiology MH - Cells, Cultured MH - Cloning, Molecular MH - Fish Diseases/immunology/microbiology MH - Fish Proteins/genetics/*immunology MH - Gene Expression Regulation MH - Head Kidney/cytology/immunology MH - Inflammation/*genetics MH - Interleukin-10/genetics/immunology MH - Interleukins/genetics/*immunology MH - Leukocytes/immunology/microbiology MH - Recombinant Proteins/genetics/immunology OTO - NOTNLM OT - Anti-bacterial activity OT - Anti-inflammatory property OT - Grass carp OT - Il-21 OT - Protein release EDAT- 2020/02/06 06:00 MHDA- 2020/12/01 06:00 CRDT- 2020/02/05 06:00 PHST- 2019/09/17 00:00 [received] PHST- 2020/01/27 00:00 [revised] PHST- 2020/01/28 00:00 [accepted] PHST- 2020/02/06 06:00 [pubmed] PHST- 2020/12/01 06:00 [medline] PHST- 2020/02/05 06:00 [entrez] AID - S1050-4648(20)30067-X [pii] AID - 10.1016/j.fsi.2020.01.059 [doi] PST - ppublish SO - Fish Shellfish Immunol. 2020 Apr;99:19-26. doi: 10.1016/j.fsi.2020.01.059. Epub 2020 Jan 31.